Abstract P1-01-04: Comparing the Effects of TC and Anthracycline-based Chemotherapy in Women with Breast Cancer HER2 Negative Treated in the Adjuvant Setting – An individual Patient Meta-Analysis
Authors: Danilo Giffoni M. M. Mata, Mary Smowton
Journal: Cancer Research (2023)

Abstract Background: Among women, breast cancer is the most common diagnosis of non-skin cancer and the fifth cause of oncological-related death worldwide. Adjuvant chemotherapy has been shown to extend overall survival (OS) and disease-free survival (DFS). Anthracyclines are cytotoxic regimens largely used in breast cancer, mainly in patients with risk factors or high burden of disease. The docetaxel and cyclophosphamide (TC) regimen is a Taxane-based treatment, and is an alternative option when anthracyclines are not indicated. However, anthracyclines have a myriad of adverse effects including alopecia, cardiac-related side effects and myelotoxicity. The question that remains is in which breast cancer population anthracycline chemotherapy should be omitted. Methods: A literature search was performed in Embase, Medline, and the Cochrane Libraries up to February 28 2022. We conducted an individual patient-level meta-analysis of 11,902 participants of 7 randomised controlled trials. The target population was adult women, with a histologically confirmed HER2 negative, stage I-III breast cancer who were treated with TC versus anthracycline-based chemotherapy in adjuvant setting under randomised-controlled trials. To analyse OS and DFS, we utilized the generic inverse variance method for time-to-event outcomes using hazard ratio (HR). A sensitivity analysis of risk of bias (ROB) was undertaken to examine the effects of high/moderate risk studies on each study endpoint. The assessment of certainty of evidence was conducted based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Results: With a median follow up of 60 months, the pooled analysis from 7 studies with available data on OS, and from 6 studies on DFS. From a total of 11,778 there was a total of 288 and 281 events of death in the TC and in the anthracycline-based chemotherapy groups, respectively. The analysis of OS revealed HR 1.01, 95% CI (0.86 – 1.19), p = 0.88; high certainty of evidence. From a total of 11,902 participants, there were 639 and 595 recurrence events in the TC and in the anthracycline-based chemotherapy groups, respectively. The analysis of DFS revealed HR 1.07, 95% CI 0.95-1.22, p=0.26; moderate certainty of evidence. No relevant absolute risk of death or recurrence events were found between the two treatments. In the quality of evidence assessment, the heterogeneity across all the studies is likely not more than what is due to chance (i2&amp;lt; 14%). The risk of bias was not a serious concern, and the publication bias was undetected for the endpoints OS and DFS. Conclusion: In this study population, TC chemotherapy likely results little to no difference in OS or DFS compared to anthracyclines-based chemotherapies. Despite the large number of participants and minimum heterogeneity across all the studies, there was no evidence of significant benefit or harm between the treatments. Overall, there is a high to moderate quality of evidence that adjuvant TC chemotherapy does not increase OS or DFS when compared to anthracycline-based chemotherapy in patients with breast cancer HER2-negative. Albeit the choice between the two chemotherapies would need to be balanced considering the specific side-effects that each treatment is likely to cause. Citation Format: Danilo Giffoni M. M. Mata, Mary Smowton. Comparing the Effects of TC and Anthracycline-based Chemotherapy in Women with Breast Cancer HER2 Negative Treated in the Adjuvant Setting – An individual Patient Meta-Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-01-04.